The present study was designed to evaluate the cardioprotective potential of aqueous leaf extract of Azadirachta indica A. Juss. (AI) on the basis of haemodynamic, biochemical and histopathological parameters in isoprenaline induced myocardial infarction in rats and to compare with vitamin E, a known cardioprotective antioxidant. A significant (p<0.01) decrease in mean arterial blood pressure (MAP), systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP) and increase in heart rate (HR) were observed in isoprenaline control group. Isoprenaline showed significant decrease in the level of cardiac marker enzymes [Lactate dehydrogenase (LDH) and Serum Glutamate Oxalotransaminase (SGOT)] in the heart homogenate with a corresponding increase in their level in serum. In vitamin E control group significant (p<0.05) increase in LDH in heart homogenate and decrease of SGOT and LDH in serum was observed. In isoprenaline control group, significant (p<0.01) increase in total cholesterol and triglycerides levels while decrease in high-density lipoproteins (HDL) was observed. On histopathological examination, myocardial damage in isoprenaline control group further confirmed cardiotoxic effect of isoprenaline. Our data showed that AI (250, 500 and 1000 mg/kg, p.o.) and vitamin E (100 mg/kg, p.o.) significantly restores most of the haemodynamic, biochemical and histopathalogical parameters. Finally we concluded that AI leaf extract exerts equipotent cardioprotective activity in the experimental model of isoprenalin induced myocardial necrosis in rats as compared to vitamin E, a known cardioprotective antioxidant.